Fused pyrimidine derivatives and antiatherosclerotic methods of treatment with them

ABSTRACT

An optically active or racemic fused pyrimidine derivative of the formula I ##STR1## has pharmaceutical activity in decreasing serum lipids, cholesterol deposits and, in general, against atherosclerosis.

CROSS REFERENCE TO RELATED APPLICATION

The application is a division of Ser. No. 765,595 filed Feb. 4, 1977, now U.S. Pat. No. 4,123,533.

DESCRIPTION OF THE INVENTION

The present invention relates to new optionally racemic or optically active fused pyrimidine derivatives of the formula ##STR2## or the salts thereof, wherein n=0, 1, 2 or 3; m=0, 1 or 2

R is hydrogen, optionally (substituted i.e. substituted or unsubstituted) amino, optionally substituted alkyl, optionally substituted hydroxyl, optionally substituted aryl, optionally substituted aralkyl, carboxyl or a group derived from the carboxyl group;

R¹ is hydrogen, optionally substituted alkyl group or

R and R¹ together form a --(CH═CH)₂ -chain, wherein the dotted line represents an optional valency bond;

R² stands for a hydrogen atom, a hydroxyl, alkoxy, mercapto, O-acyl or an optionally substituted amino group;

R³ is hydrogen, or optionally together with R² represents a valency bond;

R⁴ and R⁵ independently represent a hydrogen atom or together form a valency bond;

R⁶ is hydrogen, optionally substituted aryl, optionally substituted heterocyclic, or carboxyl, a group derived from the carboxyl group or a trihalomethyl group;

R⁷ and R⁸ independently represent a hydrogen atom or together form a valency bond;

R⁹ is hydrogen, optionally substituted hydroxyl, optionally substituted amino, alkylthio, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, carboxyl, a group derived from the carboxyl group, a heterocyclic group containing nitrogen being attached to the pyrimidine ring through a nitrogen atom,

R¹⁰ is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted amino, carboxyl group, cyano group, a group derived from the carboxyl group, an optionally substituted acyl group; and

R and R together can form a --(CH₂)_(p) -chain, wherein p represents a number from 3 through 10,

R¹¹ stands for an oxygen or sulfur atom or an R¹² --N═ -group, wherein R¹² represents a hydrogen atom or an acyl group.

The new optionally racemic or optically active fused pyrimidine derivatives provided by the invention and the salts thereof may be prepared according to the invention

(a) by reacting an optionally racemic fused pyrimidine derivative of the formula ##STR3## wherein R, R¹, R⁹, R¹⁰, R¹¹, n and the dotted line have the same meaning as defined above, with an aldehyde of the formula

    R.sup.6 --(CH--CH).sub.m --CHO                             (III)

wherein R and m have the same meaning as defined above, and optionally transforming the thus obtained fused pyrimidine derivative of the formula I, in which R⁴ and R⁵ as well as R⁷ and R⁸, respectively together form a chemical bond and R² stands for a hydroxyl group, R³ stands for a hydrogen atom, by dehydration into a fused pyrimidine derivative of the formula I, in which R² and R³ together form a valency bond; or

(b) by reacting an optionally optically active fused pyrimidine derivative of the formula II with an aldehyde derivative of the formula ##STR4## wherein R¹³ and R¹⁴ may be identical or different, thus may stand for a hydroxy, alkoxy, an optionally substituted amino, O-acyl or --SO₃ Na group, or

R¹³ and R¹⁴ together may form a ═S or ═N-R¹⁵ group,

wherein R represents a hydrogen atom, an alkyl or optionally substituted aryl group, and optionally transforming the thus obtained optionally optically active fused pyrimidine derivative of the formula I, in which

R⁴ and R⁵ as well as R⁷ and R⁸, respectively together form a valency bond, and R² represents a hydroxyl, alkoxy, optionally substituted amino, --O-acyl, mercapto group,

R³ stands for a hydrogen atom, by splitting off a compound of the formula R² H, wherein R² stands for a hydroxyl, alkoxy, optionally substituted amino, --O-acyl, mercapto group, into an optionally optically active fused pyrimidine derivative of the formula I, in which R² and R³ together form a valency bond, and if desired, by transforming groups R⁶, R⁹, R¹⁰ and R¹¹ into other R⁶, R⁹, R¹⁰ and R¹¹ groups, by per se known methods and/or by saturating the valency bonds formed by the attachment of R² and R³, R⁴ and R⁵ as well as R⁷ and R⁸, respectively by hydrogenation in an optional order, gradually or simultaneously and optionally by transforming the thus obtained optionally optically active fused pyrimidine derivative of the formula I into its acid addition salts with a pharmaceutically acceptable inorganic or organic acid, or into its salts with a pharmaceutically acceptable inorganic or organic base and/or, if desired, setting it free from its salt or transforming it into an other salt of same, and if desired preparing optically active compounds of the formula I by resolution of the racemic compound of the formula I or by using optically active starting materials in step (a) or (b).

Process variants (a) and (b) can be performed in a suitable solvent or without any solvent, preferably at a temperature from -20° C. to 250° C.

As solvents there may be used protic, apolar or dipolar aprotic solvents or the mixtures thereof.

Suitable protic solvents are the following: alkanols having 1 to 6 carbon atoms, e.g. methanol, ethanol, iso-propanol, glycerin etc.;

aliphatic carboxylic acids, e.g. formic acid, acetic acid; formamide etc.

As apolar solvent there may be used hydrocarbons, e.g. benzene, toluene, xylene etc.; chlorinated hydrocarbons, e.g. chloroform, carbontetrachloride, chlorobenzene etc.; ethers, e.g. diethylether, tetrahydrofurane, dioxane etc.

As dipolar solvents there may be used dimethyl formamide, dimethyl acetamine, dimethyl sulfoxide, ketones, e.g. acetone, ethyl methyl ketone etc.; nitro benzene; aceto nitrile; hexamethyl phosphorous triamide etc.

Suitably chosen mixtures of the above-listed solvents can be also applied.

When carrying out process variants (a) and (b) if desired, also basic or acidic catalysts can be used. Also the suitably chosen solvent itself may act as a catalyst. Thus solvents such as acetic acid or formic acid may perform a double role, since they may act as acidic catalysts and as solvents at the same time.

Additionally acidic catalysts may be applied such as inorganic or organic acids, e.g. hydrochloric acid, sulphuric acid, phosphoric acid, acetic acid etc.

As basic catalysts there may be used piperidine, diethyl amine and bifunctional catalysts such as piperidine acetate and pyridine, which are able to function as acidic and basic catalysts as well.

If desired, the reaction of process variant (a) and (b) respectively can be conducted also in such a way that instead of the addition-products, i.e. the compounds of the formula I, in which R² stands for a hydroxyl, mercapto, alkoxy, optionally substituted amino group and R³ stands for a hydrogen atom, the condensation-products, i.e. pyrimidine derivatives of the formula I in which R² and R³ together form a valency bond, are obtained.

If required R⁶ can be transformed into a different R⁶ substituent by per se known methods. Thus, a carboxyl R⁶ may be transformed into the corresponding ester group with a suitable alcohol. The esterification may be carried out by the methods known in the art for this purpose. For example the reaction preferably can be accomplished by bubbling dry hydrogen chloride gas through the alcohol solution, when esterification takes place, or by heating the mixture of carboxylic acid and alcohol in the presence of concentrated sulphuric acid, and eliminating the formed water by axeotropic distillation, with benzene or chloroform. A carboxyl R⁶ can be transformed, if desired, also to an acid amide through a suitable active ester, prepared by means of triethylamine or chloroformic acid, with ammonia or to an N-substituted acid amide group with other amines.

If R⁶ stands for an ester group, it can be converted into another ester with a different kind of alcohol, preferably in the presence of hydrogen chloride, or can be transformed into an acid amide group with ammonia, for example in an alcohol solution, into a carbohydrazide group with hydrazine hydrate and into an N-substituted acid amine group with amines.

An optionally substituted acid amide group can be prepared also by transforming the carboxyl R⁶ into an acid halide group by means of thionyl chloride, phosphorous oxychloride, phosphorous pentachloride etc. and reacting the obtained compound with an optionally substituted amine or with ammonia.

If R⁶ stands for an acid amide group it can be transformed into a nitrile group by water. The water may be extracted for example using phosphorous oxychloride, phosphorous pentoxide, thionyl chloride etc.

If R⁶ represents a nitrile group, it can be transformed into an amidine group with ammonia, into an acid amide group with water and into a thioacid amide group with hydrogen sulphide.

If desired, an ester, acid amide or nitrile R⁶ may be transformed into a carboxy group by acidic or alkaline hydrolysis. The obtained carboxyl group, if desired, can be removed when a hydrogen atom remains. The decarboxylating reaction may be carried out under heating, preferably in quinoline, polyphosphoric acid etc.

The substituents represented by R⁹ can be transformed into different substituents by methods known in the art. For example the ester, acid amide and nitrile groups may be subjected to the above-described transformations.

If desired, also the substituents represented by R¹⁰ can be transformed into different substituents. For example if R¹⁰ stands for carboxyl, ester, acid amide or nitrile groups, it can be subjected to the transformations described in connection with R⁶.

If desired, the substituents represented by R¹¹ can be transformed into a different substituent by methods known in the art. For example if R¹¹ stands for an oxygen atom, it can be reacted with phosphorous pentasulphide in pyridine, when a sulphur atom is obtained; or if R¹¹ represents an ═NH group, it may be acylated with an acid halogenide or acid anhydride preparing an ═N-acyl group; or an ═N-R¹² group represented by R¹¹ can be transformed into an oxygen atom with alkaline hydrolysis.

The obtained compounds of the formula I, if desired, can be transformed into their salts with pharmaceutically acceptable acids. As acids there may be used for example hydrochloric acid, hydrogen bromide, sulphuric acid, phosphorous acid, lactic acid, tartaric acid, maleic acid, nicotinic acid etc.

In the case where at least one of the substituents represented by R⁶, R⁹ or R¹⁰ is a carboxyl group or a group derived from a carboxyl acid also the salts of the compounds of the formula I prepared with bases can be prepared.

There can be advantageously prepared the salts of the compounds of the formula I formed with alkali metals, preferably with sodium, potassium; with alkali earth metals, preferably with calcium, magnesium, with aluminium, vanadium, ethylene diamine, 2-aminoethanol, 2-dimethylamino-ethanol, diidopropyl amine, etc.

The present invention includes also the geometric and optical isomers of the fused pyrimidine derivatives of the formula I.

The optically active compounds of the formula I can be prepared by subjecting a racemic compound of the formula I to resolution by methods known per se or by using an optically active starting material in reactions (a) or (b).

The term "optionally substituted hydroxyl group" as used herein and hereinbefore indicates a hydroxyl group, an alkoxy group having one to 6 carbon atoms, preferably a methoxy, ethoxy group, an aralkoxy group having 7 to 12 carbon atoms, preferably a benzyloxy group, an aryloxy group having 6 to 10 carbon atoms, preferably a phenoxy group.

The term "optionally substituted amino group" represents an amino group optionally bearing one or two identical or different substituents, such as an alkanoylamino group having one to 6 carbon atoms, preferably an acetylamino or propionylamino group, an aroylamino group having 6 to 10 carbon atoms, preferably a benzoylamino group, an alkylamino group having one to 6 carbon atoms, preferably a methylamino or ethylamino group, a dialkylamino group having 1 to 6 carbon atoms, in both alkyls, preferably a dimethylamino or diethylamino group, an aralkylamino group having 7 to 12 carbon atoms, preferably a benzylamino group, an arylamino group having 6 to 10 carbon atoms, preferably a phenylamino group, a piperidyl, pyrrolidinyl or a piperazinyl group.

The term "optionally substituted alkyl group" as used herein and hereinbelow means an alkyl group having one to 6 carbon atoms, preferably a methyl, ethyl, n-propyl group etc., which may bear one or more hydroxyl groups, preferably a 1-hydroxy-ethyl group, carboxyl group or a group derived from the carboxyl acid e.g. alkoxycarbonyl, carboxamido, nitrile group etc.

The term "optionally substituted aryl group" as used herein represents a phenyl group optionally bearing one or more substituents selected from the following groups: alkyl having one to 6 carbon atoms, dialkylamino, nitro, alkoxy, methylendioxy, halogen, alkylthio having one to 6 carbon atoms, carboxyl group or a group derived from a carboxylic acid.

The term "optionally substituted aralkyl group" means an aralkyl group having 7 to 12 carbon atoms optionally substituted with one or more alkyl, alkoxy, halogen, amino, or nitro group.

The term "group derived from the carboxyl group" as used herein indicated an alkoxycarbonyl having one to 6 carbon atoms in the alkyl group, or an alkoxycarbonyl having 7 to 12 carbon atoms, optionally substituted aryloxycarbonyl having 6 to 10 carbon atoms, alkoxythiocarbonyl having one to 6 carbon atoms in the alkyl group, optionally substituted acid amide, acid hydrazide, optionally substituted amidine or nitrile.

The term "optionally substituted acid amide" as used herein means an acid amide, N-alkyl, N,N-dialkyl-, N-phenylalkyl-, N-acyl-acid amide group.

The term "optionally substituted heterocyclic group" as used herein and herein below represents five-, six- or seven-membered monocyclic; nine-, ten- or eleven-membered bicyclic, or 14-membered tricyclic heterocyclic rings containing one or more oxygen, sulphur or nitrogen atom(s) optionally substituted with one or more of the following groups: alkyl having 1 to 6 carbon atoms, nitro, alkoxy, halogen, methylenedioxy, dialkylamino.

The heterocyclic ring is preferably a furane, pyrrol, pyridyl, quinolyl ring etc.

The optionally optically active compounds of the formula II used as starting materials may be prepared according to the procedures described in our Hungarian Pat. Nos. 156,119; 158,085; 162,384; 162,373; and 166,577 as well as in our Dutch Pat. No. 7,212,286 or with other similar methods.

The starting materials having the formulas III and IV are commercially available products.

As aldehydes of the formula III there may be used preferably benzaldehyde, isovanilline, vanilline, trimethoxy benzaldehyde, o-chloro-benzaldehyde, p-chloro-benzaldehyde, glyoxylic acid monohydrate, glyoxylic acid, methylenedioxy benzaldehyde, 5-nitro-2-furane-aldehyde, 2-thiophene-aldehyde, pyridine-3-aldehyde, pyridine-2-aldehyde, pyridine-4-aldehyde, cinnamic aldehyde, o-cinnamic-aldehyde, fluoro-benzaldehyde, trifluoromethyl aldehyde, methyl benzaldehyde, furfurol, 2-pyrrol-aldehyde, 1-methyl-2-pyrrol-aldehyde, diethoxy benzaldehyde, bromo-benzaldehyde, hydroxy-benzaldehyde, veratrum aldehyde, anis aldehyde, salicyl aldehyde, dimethylamino benzaldehyde, nitro benzaldehyde, alkoxy-carbonyl benzaldehyde, phthalic aldehyde, terephthalic aldehyde, formaldehyde, chloral, bromal etc.

As compounds of the formula IV there may be used for example a hemi-acetal, acetal, acylal, geminal diamine, geminal amino alcohol, Schiff-base, geminal glycol, aldehyde sodium bisulphite, aldehyde cyanohydrine.

The compounds of the formula I possess valuable pharmaceutical properties. They are especially effective against atherosclerosis, influencing not only the serum lipids, but decreasing the quantity of the lipids, deposited in vein walls, especially cholesterin.

The compounds of formula I have favorable toxical properties. The LD₅₀ -value obtained on rabbits (p.o.) generally is over 2000 mg/kg.

The pharmaceutical activity of the compounds according to the invention was proved using various experimental set-ups. In the following Table 1 there are summarized the results obtained on cholesterin-fed rabbit atherosclerosis model (Beitr. path. Anat. 56, 379-403 (9113).

It can be seen from the data of Table 1 that compounds "C" and "D" result in a significant decrease in the serum lipid, aorta lipid and cholesterin lipid level as well.

                  TABLE 1                                                          ______________________________________                                                   Serum    Aorta                                                                              total              total                                        Dose    total  choles-                                                                              tri-   total choles-                              Substance                                                                              mg/kg   lipid  terin glyceride                                                                             lipid terin                                ______________________________________                                         Control-1                                                                              --       658    326   75    1928  331                                  Control-2                                                                              --      2374   1504  103    2575  921                                  Chlofibrate                                                                            250     1938   1137  115    2227  787                                  A       50      2309   1419  121    2496  958                                  B       50      2547   1531  190    2461  365                                  C       50      1903   1176  119    1878  353                                  D       50      1638    972   97    1355  186                                  ______________________________________                                    

To make our table synoptical we have not listed in the mathematical-statistical data.

A=6-methyl-9-(N-methyl-2-pyrrolyl)-methylene-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a) pyrimidine-3-carboxylic acid ethylester

B=6-methyl-9-chloro-phenyl)-methylene-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-3-carboxylic acid ethylester

C=6-methyl-9-(ethoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)-purimidine-3-carboxylic acid ethylester

D=6-methyl-3-ethoxycarbonyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-yl-acetic acid.

In the group "Control-1" rabbits were fed with a normal feed while the rabbits in the "Control-2" group there also received 2 g of cholesterin.

Evaluating the experiments we found that the tested compound in contrast to the Chlorofibrate did not increase the weight of the liver in test animals.

The results obtained on normolyphaemic rats are listed in the following Table 2.

                  TABLE 2                                                          ______________________________________                                                 Dose                                                                           mg/kg   Serum                                                          Substance p.o.      triglyceride                                                                               cholesterine                                   ______________________________________                                         Control   --        185.1       103                                            Chlofibrate                                                                              250       144.1       63.9                                           E         50        127.9       86.5                                           F         50        155.5       88.0                                           G         50        127.5       88.0                                           H         50        107.9       90.2                                           ______________________________________                                    

E=9-(ethoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-3-carboxylic acid ethylester

F=9-(carboxyl-methyl)-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2a)pyrimidine-3-carboxylic acid ethylester

G=9-(carboxyl-methyl)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine-3-carboxylic acid ethylester

H=9-(methoxycarbonyl-methylene)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-3-carboxylic acid methylester

For the sake of simplicity the mathematical-statistical data have been omitted also in Table 2.

Other representatives of the compounds according to the present invention show a significant central neurotic system(CNS) activity. Thus some of the compounds exhibit significant degrees of analgesic, antipyretic, antiinflammatory activity, tranquillizer narcotic potentiating activity, liver-protective, antidepressive, antibacterial or antituberculotic as well as anti-asthmatic activity.

The compounds prepared according to the invention find their application chiefly as pharmaceuticals but may be applied also as starting substances for the preparation of other, pharmaceutically active compounds.

The compounds of the formula I according to the invention may be applied in various application forms prepared by admixing them with inert, non-toxic solid or liquid diluents or carriers. The compositions may be finished as solid formulations, e.g. tablets, capsules, dragees, perl-capsules, or liquid formulations, e.g. solutions, suspension or emulsions.

The dose depends on the field of the application and of the pharmaceutical form used. Thus generally compositions containing 1 mg to 100 mg of active ingredient may be prepared.

As carriers the generally used substances, such as talcum, calcium carbonate, magnesium stearate, water, polyethylene glycolate may be employed.

The composition contain, if desired, also some other conventionally used excipients, such as emulsifiers, decomposing agents etc.

The compositions, if desired, may be finished also in forms showing retarded activity.

Further details of our invention are to be found in the following Examples.

EXAMPLE 1

The mixture of 23.6 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine and 10.6 g of benzaldehyde is stirred at 40° C. whereupon 10 ml of ethanol are added and the reaction mixture is allowed to stand overnight. The precipitated crystals are filtered off. White 3-ethoxy-carbonyl-9-(1'-hydroxy-benzyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is obtained melting after recrystallization from ethanol at 186° to 187° C.

Analysis: Calculated: C 66.65%, H 6.48%, N 8.18%: Found: C 66.72%, H 6.50%, H 8.19%.

EXAMPLE 2

According to the method described in Example 1 but using chloral or chloral hydrate as the aldehyde component 3-ethoxycarbonyl-9-(1-hydroxyl-2,2,2-trichloroethyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is obtained. Melting point after recrystallisation from ethanol: 165° to 166° C. Yield: 61%.

Analysis: Calculated: C 43.83%, H 4.47%, N 7.30%, Cl 27.70%: Found: C 43.70%, H 4.51%, N 7.39%, Cl 27.37%.

EXAMPLE 3

The mixture of 118.0 g of 3-ethoxy-carbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine and 30 g of paraformaldehyde in 1200 ml of ethanol is heated for 2 hours, whereupon 15 g of paraformaldehyde are added to the reaction mixture which is then stirred for an additional one hour. Thereafter there is added an additional 15 g portion of paraformaldehyde and the mixture is boiled for an additional one hour. The reaction mixture is evaporated, the residue is dissolved in 1200 ml of water and shaken out subsequently with benzene and chloroform. After drying the chloroform solution is evaporated, and the residue is recrystallized from ethanol twice to yield 3-ethoxycarbonyl-9,9-di-(hydroxymethyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine melting at 119° to 120° C.

Analysis: Calculated: C 56.75%, H 6.80%, N 9.45%: Found: C 56.89%, H 6.80%, N 9.40%.

EXAMPLE 4

34 g of 3-ethoxycarbonyl-9-(1'-hydroxyl-benzyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)-pyrimide are boiled in the mixture of 100 ml of ethanol and 10 ml of 15 percent by weight solution of hydrochloric acid in ethanol. Upon cooling the precipitated yellow crystals are filtered off, and recrystallized from ethanol to yield 3-ethoxycarbonyl-9-benzylidene-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine. The product does not decrease the melting point of the product prepared according to Example 5, when admixed with that.

EXAMPLE 5

23.6 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine and 10.6 g of benzaldehyde are reacted in the mixture of 10 ml ethanol and 5 ml of 15 percent by weight solution of hydrochloric acid in ethanol. The resulting 3-ethoxycarbonyl-9-(1'-hydroxyl-benzyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is transformed without separation, under further heating and stirring into the yellow 3-ethoxycarbonyl-9-benzylidene-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine. The melting point of the above compound after recrystallization from ethanol is 140° to 141° C. Yield: 70%.

Analysis: Calculated: C 70.35%, H 6.22%, N 8.64%: Found: C 70.24%, H 5.99%, N 8.60%

According to the method described in Example 5 using the appropriate starting materials the following compounds listed in Table 3 are prepared.

                                      TABLE 3                                      __________________________________________________________________________      ##STR5##                                                                                                                  M.p. °C.                                                                solvent   Analysis                                                             used for  Calculated                                                       Cata-                                                                              crystal-                                                                             Yield                                                                              Found                    No. R.sub.16    R.sub.17                                                                          R.sub.18                                                                          R.sub.19    Solvent                                                                              lyst                                                                               lization                                                                             %   C% H% N%                 __________________________________________________________________________     6.  5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         pyridine                                                                             --  194-195                                                                              85  56.82                                                                             4.77                                                                              11.69                                                                    56.75                                                                             4.79                                                                              11.80              7.  2-furyl     CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         n-propanol                                                                           --  152-154                                                                              78  64.96                                                                             5.77                                                                              8.91                                                           DMF       64.99                                                                             5.68                                                                              9.07               8.  2-pyrryl    CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethylene                                                                             HCl 246   76  65.16                                                                             6.11                                                                              13.41                                                glycol    ethanol   65.03                                                                             6.04                                                                              13.65              9.  N-methyl-2-pyrryl                                                                          CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 165-166                                                                              61  66.04                                                                             6.47                                                                              12.84                                                          ethanol   65.94                                                                             6.43                                                                              12.78              10. 3,4,5-trimethoxy-phenyl                                                                    CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 138-141                                                                              80  63.76                                                                             6.32                                                                              6.76                                                           ethanol   63.49                                                                             6.30                                                                              6.90               11. 3-hydroxy-4-methoxy-                                                                       CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 190-192                                                                              82  64.85                                                                             5.99                                                                              7.56                   phenyl                                            65.00                                                                             5.90                                                                              7.45               12. 3,4-methylenedioxy-                                                                        CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 140-142   65.21                                                                             5.47                                                                              7.60                   phenyl                                  dimethyl- 65.40                                                                             5.40                                                                              7.86                                                           formamide                          13. 3,4-dimethoxy-phenyl                                                                       CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 134-135                                                                              65  65.61                                                                             6.29                                                                              7.29                                                           ethanol   65.86                                                                             6.18                                                                              7.37               14. 4-hydroxy-phenyl                                                                           CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 240-242                                                                              88  67.05                                                                             5.92                                                                              8.22                                                           DMF       67.11                                                                             5.78                                                                              8.40               15. 4-chloro-phenyl                                                                            CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         carbontetra-                                                                         --  183-185                                                                              85  63.60                                                                             5.34                                                                              7.81                                                 chloride  n-propanol                                                                               63.42                                                                             5.12                                                                              8.00                                                                     Cl 9.88                                                                        Cl 9.78                  16. 2-phenyl-vinyl                                                                             CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         carbontetra-                                                                         --  167-169                                                                              75  71.98                                                                             6.33                                                                              7.99                                                 chloride  n-propanol                                                                               71.60                                                                             6.32                                                                              8.15               17. 4-methoxy-phenyl                                                                           CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         carbontetra-                                                                         --  114-116                                                                              61  67.78                                                                             6.26                                                                              7.90                                                 chloride  ethanol   67.58                                                                             6.28                                                                              8.02               18. 2-hydroxy-phenyl                                                                           CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         carbontetra-                                                                         --  200-201                                                                              81  67.05                                                                             5.92                                                                              8.23                                                 chloride  dioxane   66.82                                                                             6.01                                                                              8.34               19. 4-dimethyl-amino-                                                                          CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         carbontetra-                                                                         --  161-162                                                                              81  68.64                                                                             6.86                                                                              11.44                  phenyl                        chloride  ethanol   68.32                                                                             6.74                                                                              11.59              20. 2-(2-nitro-phenyl)-                                                                        CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 166-168                                                                              77  63.79                                                                             5.35                                                                              10.63                  vinyl                                   propanol  63.60                                                                             5.41                                                                              10.54              21. 2-chloro-phenyl                                                                            CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              --  138-140                                                                              50  63.60                                                                             5.34                                                                              7.81                                                           ethanol   63.81                                                                             5.29                                                                              7.88                                                                     Cl 9.88                                                                        Cl 10.02                 22. 2-nitro-phenyl                                                                             CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              HCl 158-159                                                                              50  61.78                                                                             5.19                                                                              11.38                                                          ethanol   61.63                                                                             5.15                                                                              11.58              23. 4-nitro-phenyl                                                                             CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         218-220                                                                              46  61.78                                                                             5.19                                                                              11.38                                                      sulfonic-                                                                          ethyl-    61.49                                                                             5.15                                                                              11.35                                                      acid                                                                               acetate                            24. 2-ethoxy-phenyl                                                                            CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         149-151                                                                              44  68.46                                                                             6.57                                                                              7.60                                                       sulfonic                                                                           ethanol   68.34                                                                             6.46                                                                              7.56                                                       acid                                   25. 3-nitro-phenyl                                                                             CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         151-153                                                                              46  61.78                                                                             5.19                                                                              11.38                                                      sulfonic-                                                                          ethanol   61.88                                                                             5.13                                                                              11.26                                                      acid                                   26. 3,4-dichloro-phenyl                                                                        CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         148-150                                                                              51  58.03                                                                             4.61                                                                              7.12                                                       sulfonic                                                                           ethanol   58.03                                                                             4.51                                                                              7.08                                                       acid                                   27. 3-cyano-phenyl                                                                             CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         148-  20  68.76                                                                             5.48                                                                              12.03                                                      sulfonic-                                                                          ethanol   69.08                                                                             5.36                                                                              12.07                                                      acid                                   28. 3-pyridyl   CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         108-110                                                                              37  66.86                                                                             5.30                                                                              13.00                                                      sulfonic                                                                           ethanol   66.65                                                                             5.40                                                                              12.98                                                      acid                                   29. 4-acetylamino-phenyl                                                                       CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         benzene                                                                              p-toluene-                                                                         212-214                                                                              86  64.62                                                                             6.84                                                                              9.83                                                       sulfonic                                                                           ethanol   64.60                                                                             6.80                                                                              9.89                                                       acid                                   30.***                                                                             carboxy     CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              --  167-168                                                                              73  57.53                                                                             5.52                                                                              9.58                                                           ethanol   57.65                                                                             5.48                                                                              9.70               31.*                                                                               carboxy     CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              --  168-170                                                                              72  57.53                                                                             5.52                                                                              9.58                                                           ethanol   57.45                                                                             5.70                                                                              9.57               32.**                                                                              carboxy     CH.sub.3                                                                          H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              --  169-171                                                                              74  57.53                                                                             5.52                                                                              9.58                                                           ethanol   57.62                                                                             5.46                                                                              9.72               33. phenyl      CH.sub.3                                                                          H  COOH        xylene                                                                               sulfuric                                                                           204-205                                                                              71  68.91                                                                             5.44                                                                              9.45                                                       acid                                                                               DMF       68.68                                                                             5.46                                                                              9.56               34. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  COOH        benzene                                                                              --  253-254                                                                              50  54.23                                                                             3.96                                                                              12.68                                                          DMF       54.55                                                                             3.85                                                                              12.58              35. 2-hydroxy-phenyl                                                                           CH.sub.3                                                                          H  COOH        benzene                                                                              --  235-236                                                                              67  65.38                                                                             5.16                                                                              8.97                                                           DMF       65.17                                                                             5.10                                                                              8.92               36. 2-chloro-phenyl                                                                            CH.sub.3                                                                          H  COOH        xylene                                                                               sulfuric                                                                           205       61.73                                                                             4.57                                                                              8.47                                                       acid                                                                               DMF       61.64                                                                             4.68                                                                              8.56                                                                     Cl 10.72                                                                       Cl 10.40                 37. 4-chloro-phenyl                                                                            CH.sub.3                                                                          H  COOH        benzne                                                                               --  222-223   61.73                                                                             4.57                                                                              8.47                                                           DMF       61.59                                                                             4.51                                                                              8.32                                                                     Cl 10.72                                                                       Cl 10.48                 38. N-methyl-2-pyrryl                                                                          CH.sub.3                                                                          H  COOH        benzene                                                                              --  210-211                                                                              33  64.20                                                                             5.72                                                                              14.04                                                          DMF       64.08                                                                             5.57                                                                              14.10              39. 2-nitro-phenyl                                                                             CH.sub.3                                                                          H  COOH        benzene                                                                              --  199-200                                                                              73  59.82                                                                             4.43                                                                              12.31                                                          DMF       59.72                                                                             4.47                                                                              12.21              40. 4-hydroxy-phenyl                                                                           CH.sub.3                                                                          H  COOH        benzene                                                                              --  279-280                                                                              98  65.38                                                                             5.16                                                                              8.97                                                           DMF       65.42                                                                             5.11                                                                              8.90               41. 2-pyrryl    CH.sub.3                                                                          H  COOH        benzene                                                                              --  287-288                                                                              87  63.15                                                                             5.30                                                                              14.73                                                          DMF       63.47                                                                             5.27                                                                              14.81              42. 3,4-methylene-dioxy-                                                                       CH.sub.3                                                                          H  COOH        benzene                                                                              --  247-248                                                                              85  63.53                                                                             4.74                                                                              8.23                   phenyl                                  DMF       62.98                                                                             4.75                                                                              8.23               43. carboxy     CH.sub.3                                                                          H  COOH        benzene                                                                              --  202-203                                                                              95  54.60                                                                             4.58                                                                              10.62                                                          ethanol   54.74                                                                             4.55                                                                              10.56              44. 2-(2-nitro-phenyl)-                                                                        CH.sub.3                                                                          H  COOH        benzene                                                                              --  234-235                                                                              62  62.13                                                                             4.66                                                                              11.44                  vinyl                                   DMF       62.01                                                                             4.59                                                                              11.41              45. 3-hydroxy-4-methoxy-                                                                       CH.sub.3                                                                          H  COOH        benzene                                                                              --  256-257                                                                              79  63.14                                                                             5.30                                                                              8.18                   phenyl                                  DMF       63.14                                                                             5.38                                                                              8.27               46. 3,4,5-trimethoxy-                                                                          CH.sub.3                                                                          H  COOH        benzene                                                                              --  184-185                                                                              90  62.17                                                                             5.74                                                                              7.25                   phenyl                                  DMF       62.03                                                                             5.53                                                                              7.20               47. 4-methoxy-phenyl                                                                           CH.sub.3                                                                          H  COOH        benzene                                                                              --  195-196                                                                              64  66.25                                                                             5.56                                                                              8.58                                                           DMF       66.42                                                                             5.56                                                                              8.49               48. 2-furyl     CH.sub.3                                                                          H  COOH        benzene                                                                              --  225-227                                                                              90  62.93                                                                             4.93                                                                              9.79                                                           DMF       62.84                                                                             4.88                                                                              9.77               49. 2-phenyl-vinyl                                                                             CH.sub.3                                                                          H  COOH        benzene                                                                              --  223-224                                                                              78  70.80                                                                             5.63                                                                              8.69                                                           DMF       70.86                                                                             5.50                                                                              8.75               50. 3,4-dimethoxy-phenyl                                                                       CH.sub.3                                                                          H  COOH        benzene                                                                              --  222       64.04                                                                             5.66                                                                              7.86                                                           DMF       64.30                                                                             5.61                                                                              7.73               51. 4-dimethylamino-phenyl                                                                     CH.sub.3                                                                          H  COOH        benzene                                                                              --  228-229                                                                              97  67.24                                                                             6.24                                                                              12.38                                                          DMF       67.48                                                                             6.18                                                                              12.26              52  4-hydroxy-3-methoxy-                                                                       CH.sub.3                                                                          H  COOH        benzene                                                                              --  254-255                                                                              67  63.14                                                                             5.30                                                                              8.18                   phenyl                                  DMF       62.98                                                                             5.32                                                                              8.11               53. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  CH.sub.3    benzene                                                                              acetic                                                                             183-184                                                                              46  59.80                                                                             5.02                                                                              13.95                                                      acid                                                                               ethanol   60.07                                                                             5.06                                                                              14.06              54. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  CONHN       dimethyl                                                                             --  288-290                                                                              53  51.28                                                                             3.44                                                                              17.94                                     ##STR6##   formamide DMF       50.86                                                                             3.47                                                                              17.76              55. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  CONH.sub.2  methanol                                                                             --  278-280                                                                              68  54.54                                                                             4.27                                                                              16.96                                                          DMF       54.50                                                                             4.15                                                                              16.91              56. 5-nitro-furyl                                                                              H  H  C.sub.6 H.sub.5                                                                            acetone                                                                              HCl 245-246                                                                              61  65.32                                                                             4.33                                                                              12.03                                                          DMF       65.25                                                                             4.02                                                                              11.97              57. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          H  H           formamide                                                                            --  196   80  58.23                                                                             4.57                                                                              14.63                                                          dioxane   56.15                                                                             4.49                                                                              14.60              58. 5-nitro-2-furyl                                                                            H  H  COOC.sub.2 H.sub.5                                                                         chloroform                                                                           --  240   82  55.65                                                                             4.38                                                                              12.17                                                          DMF       55.45                                                                             4.28                                                                              12.12              59. 5-nitro-2-furyl                                                                            CH.sub.3                                                                          CH.sub.3                                                                          H           ethanol                                                                              HCl 235   63  59.80                                                                             5.02                                                                              13.95                                                          n-propanol                                                                               60.07                                                                             5.15                                                                              14.01              60. 5-nitro-2-furyl                                                                            H  CH.sub.3                                                                          H           ethanol                                                                              HCl 217   66  58.25                                                                             4.56                                                                              14.63                                                          ethanol   58.03                                                                             4.50                                                                              14.40              61. carboxy     CH.sub.3                                                                          H  CONH.sub.2  ethanol                                                                              --  242   85  54.75                                                                             4.98                                                                              15.96                                                          DMF       54.60                                                                             5.09                                                                              15.83              62. carboxy     H  H  COOC.sub.2 H.sub.5                                                                         ethanol                                                                              --  170-171                                                                              81  56.11                                                                             5.07                                                                              10.07                                                          ethanol   56.18                                                                             5.10                                                                              9.85               63. carboxy     CH.sub.3                                                                          H  COOCH.sub.3 ethanol                                                                              --  160-162                                                                              90  56.11                                                                             5.07                                                                              10.07                                                          ethanol   55.99                                                                             5.01                                                                              9.82               64. carboxy     CH.sub.3                                                                          H                                                                                  ##STR7##   ethanol                                                                              --  205-206 ethanol                                                                      85  58.82 58.91                                                                       5.92 6.02                                                                         9.16 9.09          65. carboxy     CH.sub.3                                                                          H  COO(CH.sub.2).sub.2 CH.sub.3                                                               ethanol                                                                              --  167-168                                                                              80  58.82                                                                             5.92                                                                              9.16                                                           ethanol   58.42                                                                             5.87                                                                              9.19               66. carboxy     CH.sub.3                                                                          H  COO(CH.sub.2).sub.3 CH.sub.3                                                               ethanol                                                                              --  140-141   59.99                                                                             6.29                                                                              8.75                                                           ethanol   60.02                                                                             6.15                                                                              8.73               67. carboxy     CH.sub.3                                                                          H  CH.sub.2 COOC.sub.2 H.sub.5                                                                benzene                                                                              --  123-124   59.40                                                                             4.99                                                                              9.24                                                           ethyl-    59.56                                                                             5.07                                                                              9.20                                                           acetate                            68. carboxy     CH.sub.3                                                                          H  H           benzene                                                                              --  213-214                                                                              60  59.99                                                                             5.49                                                                              12.72                                                          ethanol   59.94                                                                             5.52                                                                              12.53              69. carboxy     CH.sub.3                                                                          H  CH.sub.3    benzene                                                                              --  239-240                                                                              40  61.53                                                                             6.03                                                                              11.96                                                          ethanol   61.58                                                                             5.81                                                                              12.01              70. carboxy     CH.sub.3                                                                          H  C.sub.6 H.sub.5                                                                            benzene                                                                              --  210-211                                                                              54  68.44                                                                             6.08                                                                              9.39                                                           methanol  68.56                                                                             6.12                                                                              9.38               71. carboxy     CH.sub.3                                                                          H  CN          ethanol                                                                              --  242-243                                                                              45  58.77                                                                             4.52                                                                              17.13                                                          DMF-      59.00                                                                             4.47                                                                              17.18                                                          ethanol                            72. carboxy     CH.sub.3                                                                          CH.sub.3                                                                          H           ethanol                                                                              HCl 227   65  61.53                                                                             6.02                                                                              11.96                                                                    61.84                                                                             6.22                                                                              11.82              73. carboxy     H  CH.sub.3                                                                          H           ethanol                                                                              HCl 254   45  59.99                                                                             5.49                                                                              12.72                                                                    59.83                                                                             5.49                                                                              12.61              __________________________________________________________________________       *[α].sub.D.sup.20 = -217° (c = 2,methanol)                       **[α].sub.D.sup.20 = +216° (c = 2,methanol)                       ***by the preparation of compounds wherein R.sup.16 is carboxy, as             aldehyde component glyoxilic acid or glyoxilic acid monohydrate may be         used.                                                                    

EXAMPLE 74

23.6 g of 3-ethoxycarbonyl-7-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine and 10.0 g of glyoxylic acid monohydrate are reacted and the obtained 3-ethoxycarbonyl-7-methyl-9-(carboxy-(hydroxymethyl)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is heated in 150 ml ethanol under stirring for 3 hours. After cooling the crystals are filtered off and recrystalized from ethanol. Thus 3-ethoxycarbonyl-7-methyl-9-(carboxy-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine melting at 110° to 112° C. is obtained.

Yield: 51%.

Analysis: Calculated: C 57.53%, H 5.52%, N 9.58%: Found: C 57.32%, H 5.60%, N 9.56%.

EXAMPLE 75

The benzene mother liquor obtained by example 17 is evaporated in vacuo. The residue is dissolved in 10 ml of ethanol whereupon 15 ml of ethanol containing 16% hydrochloric acid are added. The 3,6-dimethyl-9-(5-nitro-2-furfurylidene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidinium-hydrochloride melts at 215°-216° C. after recrystallization from ethanol.

Analysis: Calculated: C 53.34%, H 4.78%, N 12.44%, Cl 10.50%: Found: C 53.22%, H 4.83%, N 12.55%, Cl 10.55%.

EXAMPLE 76

3-ethoxycarbonyl-9-(1'-phenylamino-benzyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine obtained by reacting 47.2 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine and 36.2 g of benzalaniline is stirred in a water bath for 8 hours, whereupon 3-ethoxycarbonyl-9-benzylidene-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is obtained accompanied by the formation of aniline. The reaction mixture is dissolved in 300 ml of benzene and shaken out with 5 percent by weight solution of hydrochloric acid in water. The benzene phase is dried, evaporated and the residue is recrystallized from ethanol twice. Yellow 3-ethoxycarbonyl-9-benzylidene-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine melting at 138° to 139° C. is obtained. The product does not give any decrease in the melting point of the product prepared according to Example 5 when admixed therewith.

EXAMPLE 77

55.6 g of 3-ethoxycarbonyl-9-(carboxy-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine are hydrogenated in 500 ml of ethanol in the presence of 20 g of 9 percent by weight Pd/C catalyst containing metal. When 1 mole of hydrogen has been used up, the catalyst is removed from the reaction mixture by filtration and the solution is evaporated under reduced pressure. The residue is recrystallized from ethanol. 3-ethoxycarbonyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid melting at 156° to 157° C. is obtained.

Yield: 57%

Analysis: Calculated: C 55.71%, H 5.75%, N 10.00%: Found: C 55.51%, H 5.62%, N 10.07%.

According to the method described in Example 77 using the appropriate starting material the following compounds listed in Table 4 are obtained.

                                      TABLE 4                                      __________________________________________________________________________      ##STR8##                                                                                                 Analysis                                                            M.p. °C.                                                                           Calculated                                                          solvent used                                                                              Found                                               No.                                                                               R.sub.18                                                                          R.sub.19  for cryst.                                                                            Yield                                                                              C% H% N%                                            __________________________________________________________________________        H  COOC.sub.2 H.sub.5                                                                       153-154                                                                               68  57.14                                                                             6.17                                                                              9.52                                                          ethanol    57.02                                                                             6.22                                                                              9.54                                          79.*                                                                              H  COOC.sub.2 H.sub.5                                                                       130-132                                                                               75  57.14                                                                             6.17                                                                              9.52                                                          ethanol    57.23                                                                             6.20                                                                              9.51                                          80.**                                                                             H  COOC.sub.2 H.sub.5                                                                       133-134                                                                               68  57.14                                                                             6.17                                                                              9.52                                                          ethanol    57.10                                                                             6.30                                                                              9.60                                             H  C.sub.6 H.sub.5                                                                          162-164                                                                               89  68.44                                                                             6.08                                                                              9.39                                                          ethanol    68.06                                                                             6.00                                                                              9.28                                             H  COOCH.sub.3                                                                              215    80  55.71                                                                             5.75                                                                              9.99                                                                     55.65                                                                             5.72                                                                              10.03                                            H  COOCH(CH.sub.3).sub.2                                                                    148    60  58.43                                                                             6.54                                                                              9.09                                                          ethanol    58.05                                                                             6.57                                                                              8.98                                             H  COO(CH.sub.2).sub.2 CH.sub.3                                                             137    57  58.43                                                                             6.54                                                                              9.09                                                          ethanol    58.20                                                                             6.34                                                                              8.94                                             H  H         178    65  59.45                                                                             6.35                                                                              12.60                                                         ethanol    59.36                                                                             6.43                                                                              12.71                                            CH.sub.3                                                                          H         175-176                                                                               68  61.00                                                                             6.83                                                                              11.86                                                         ethanol    60.96                                                                             6.86                                                                              11.90                                         __________________________________________________________________________      *[α].sub.D.sup.20 = -164° (c = 1, methanol)                       **[α].sub.D.sup.20 = +165° (c = 1, methanol)                

EXAMPLE 87

34.0 g of 3-ethoxycarbonyl-9-(carboxy-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine are hydrogenated in 600 ml of ethanol in the presence of 20 g of 9 percent by weight Pd/C catalyst containing metal. When 2 moles of hydrogen have been used up, the catalyst is filtered off from the reaction mixture and the mixture is evaporated under reduced pressure. The residue is recrystallized from ethanol. 3-ethoxycarbonyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid melting at 205° C. is obtained.

Analysis: Calculated: C 55.31%, H 6.43%, N 9.92%: Found: C 55.25%; H 6.32%, N 10.03%.

EXAMPLE 88

29.4 g of 3-methoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid methylester are dissolved in methanol at 10° C. The aqueous solution of 5 g of sodiumborohydride is added to the solution dropwise. The precipitated crystals are filtered off, and washed with water and then with methanol. 3-methoxycarbonyl-6-methyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid methylester is obtained. Yield: 89%.

The melting point after recrystallization from dimethylformamide is 225° to 226° C. (decomp.)

Analysis: Calculated: C 56.75%, H 6.80%, N 9.45%: Found: C 56.74%, H 6.89%, N 9.63%.

EXAMPLE 89

According to the method described in Example 88 but starting from 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid ethyl ester. 3-ethoxycarbonyl-6-methyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid ethyl ester is obtained. Melting point after recrystallization from dimethylformamide 206° C. Yield: 56%.

Analysis: Calculated: C 59.25%, H 7.46%, N 8.64%: Found: C 59.03%, H 7.56%, N 8.63%.

EXAMPLE 90

55.6 g of 3-ethoxycarbonyl-9-(carboxy-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine are suspended in 400 ml of ethanol. The reaction mixture is saturated with hydrogen chloride gas under stirring and external cooling, then allowed to stand at room temperature overnight. Ethanol is distilled off under reduced pressure and the obtained residue is recrystallized from ethanol. 3-ethoxycarbonyl-9-(ethoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine melting at 120° to 121° C. is obtained. Yield: 90%.

Analysis: Calculated: C 58.82%, H 5.92%, N 9.15%: Found: C 58.72%, H 5.70%, N 9.29%.

According to the method described in Example 90 using the appropriate starting material the following compounds listed in Table 5 are prepared.

                                      TABLE 5                                      __________________________________________________________________________      ##STR9##                                                                                                  Analysis                                                                M.p. °C.                                                                       Calculated                                                              solvent used                                                                          Found    Yield                                     No.                                                                               R.sub.18                                                                          R.sub.19                                                                             X      Y for cryst.                                                                            C% H% N% %                                         __________________________________________________________________________        H  COOC.sub.2 H.sub.5                                                                   valency bond                                                                            133-135                                                                               59.99                                                                             6.29                                                                              8.75                                                                              82                                                             isopropanol                                                                           59.48                                                                             6.22                                                                              9.01                                         92.*                                                                              H  COOC.sub.2 H.sub.5                                                                   valency bond                                                                            121-123                                                                               59.99                                                                             6.29                                                                              8.75                                                                              69                                                             isopropanol                                                                           59.78                                                                             6.32                                                                              8.74                                         93.**                                                                             H  COOC.sub.2 H.sub.5                                                                   valency bond                                                                            122-123                                                                               59.99                                                                             6.29                                                                              8.75                                                                              65                                                             isopropanol                                                                           60.12                                                                             6.20                                                                              8.79                                            H  H     valency bond                                                                            120    62.89                                                                             6.50                                                                              11.28                                                                             68                                                             ethanol                                                                               62.95                                                                             6.51                                                                              11.19                                           H  C.sub.6 H.sub.5                                                                      valency bond                                                                            129-131                                                                               70.35                                                                             6.22                                                                              8.64                                                                              85                                                             isopropanol                                                                           70.62                                                                             6.30                                                                              8.76                                            CH.sub.3                                                                          H     valency bond                                                                            124-126                                                                               64.11                                                                             6.92                                                                              10.68                                                                             74                                                             ethanol                                                                               64.23                                                                             6.94                                                                              10.80                                           H  COOC.sub.2 H.sub.5                                                                   H      H oil    59.63                                                                             6.88                                                                              8.69                                                                              65                                                                    59.90                                                                             6.80                                                                              8.61                                            H  H     H      H 78-79  62.89                                                                             6.50                                                                              11.28                                                                             84                                                             petrol-                                                                               62.38                                                                             6.42                                                                              11.12                                                             ether                                                        CH.sub.3                                                                          H     H      H 71-73  63.62                                                                             7.63                                                                              10.60                                                                             60                                                             petrol-                                                                               63.76                                                                             7.72                                                                              10.61                                                             ether                                                     __________________________________________________________________________      *[α].sub.D.sup.20 = -215° (c = 2, methanol)                       **[α].sub.D.sup.20 = +215.5° (c = 2, methanol)              

EXAMPLE 100

14.7 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid are heated in the mixture of 23 g of ethanol and 5 ml of sulphuric acid for 5 hours, whereupon the ethanol is distilled off under reduced pressure and the residue is poured on ice and shaken out with chloroform. The chloroform solution is dried and evaporated under reduced pressure. Ethylacetate is distilled through the residue. 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine-9-acetic acid ethylester is obtained in the form of non-crystallizing yellow oil. Yield: 50%.

Analysis: Calculated: C 59.62%, H 6.88%, N 8.69%: Found: C 60.02%, H 6.90%, N 8.65%.

EXAMPLE 101

According to the process described in Example 100 but starting from 3-ethoxycarbonyl-6-methyl-9-(carboxymethylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine 3-ethoxycarbonyl-6-methyl-9-(ethoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is obtained. The product does not give any decrease in melting point when admixed with one product of Example 91.

EXAMPLE 102

14.7 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid are heated in the mixture of 4.6 g of ethanol, 0.25 g of sulphuric acid and 25 ml of chloroform and the water deliberating during the esterification is continuously collected in a water separator.

The reaction mixture is shaken out with 2-fold 30 ml of 5 percent by weight sodium carbonate solution, dried and the chloroform is distilled off under reduced pressure. Thus 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine-3-acetic acid ethyl ester is obtained in the form of non-crystallizing oil.

Analysis: Calculated: C 59.62%, H 6.88%, N 8.69%: Found: C 59.70%, H 6.98%, N 8.54%.

EXAMPLE 103

According to the process described in Example 102 but starting from 3-ethoxycarbonyl-6-methyl-9-(carboxymethylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-3-ethoxycarbonyl-6-methyl-9-(ethoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine melting at 134° to 135° C. is obtained. The product does not give any decrease in the melting point when admixed with the product of the Example 91 and 100, respectively.

EXAMPLE 104

43.84 g of 3-ethoxycarbonyl-6-methyl-9-(carboxymethylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine are suspended in 400 ml of methanol. The mixture is saturated with hydrogen chloride gas under stirring, at 0° to 5° C. and the reaction mixture is allowed to stand in a refrigerator overnight. The reaction mixture is evaporated under reduced pressure and the residue is admixed with 200 ml of water. The precipitated crystals are filtered off, washed with water and recrystallized from n-propanol. 3-methoxy-carbonyl-6-methyl-9-(methoxycarbonyl-methylene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido-(1,2a)pyrimidine is obtained. Melting point: 135° to 137° C.

Yield: 80%.

Analysis: Calculated: C 57.53%, H 5.52%, N 9.58%: Found: C 57.66%, H 5.34%, N 9.60%.

EXAMPLE 105

50 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-yl-acetic acid are dissolved in methanol and gaseous hydrogen chloride is introduced for 5 hours at -10° C. The reaction mixture is allowed to stand at room temperature over night and evaporated in vacuo. The residue is dissolved in water and the pH of the solution is adjusted to 7 with aqueous sodium hydrogen carbonate solution. After extraction with benzene and drying and evaporation of the extract 3-methoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid methyl ester are obtained.

Mp.: 101°-103° C. after recrystallization from ethyl acetate.

Yield: 67%.

Analysis: Calculated: C 57.14%, H 6.17%, N 9.52%: Found: C 57.57%, H 6.34%, N 9.50%.

EXAMPLE 106

58.8 of 3-methoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid methyl ester are stirred with aqueous sodium hydroxide solution. The reaction mixture is neutralized with hydrochloric acid. The precipitated crystals are filtered off. Thus 3-carboxy-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)-pyrimidine-9 acetic acid are obtained. Yield: 75%.

Mp.: 190° C., decomposition, after recrystallization from n-propanol.

Analysis: Calculated: C 54.13%, H 5.30%, N 10.52%: Found: C 54.17%, H 5.32%, N 10.31%.

EXAMPLE 107

0.65% of magnesium is reacted with 20 ml of ethanol in the presence of 0.1 g of iodine as catalyst. To the magnesiumethylate solution thus obtained 14.7 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetic acid and 300 ml of ethanol are added. The reaction mixture is heated to boiling, filtered off and the filtrate is evaporated in vacuo. Thus 13.0 g of crude magnesium-3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-acetate are obtained.

M.p: above 360° C. decomposition, after recrystallization from a mixture of ethanol and ethyl acetate.

Analysis: Calculated: C 55.05%, H 5.60%, N 9.17%: Found: C 54.18%, H 5.68%, N 8.93%.

EXAMPLE 108

50 g of 3-(ethoxycarbonyl-methyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine are reacted with 28.2 g of 5-nitro-2-furfurol and the obtained 3-(ethoxycarbonyl-methyl)-6-methyl-9-(5-nitro-2-furyl)-hydroxymethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine is boiled without separation in the mixture of 600 ml of benzene and 2 ml of 16 percent weight solution of hydrochloric acid in ethanol in a flask equipped with a water separator, and then the reaction mixture is evaporated under reduced pressure. The obtained residue is recrystallized from ethanol containing hydrochloric acid twice. Thus 3-(ethoxycarbonyl-methyl)-6-methyl-9-(5-nitro-2-furfurylidene)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidinium hydrochloride is obtained.

Yield: 72%.

Analysis: Calculated: C 52.76%, H 4.92%, N 10.43%, Cl 8.65%: Found: C 52.98%, H 4.86%, N 10.26%, Cl 8.63%.

EXAMPLE 109

750 g of 3-ethoxycarbonyl-6-methyl-4-oxo-4H-pyrido-(1,2a)pyrimidine-9-yl-acetic acid are homogenized with 1050 g of crystalline cellulose and 140 g of amylopectine. Granules are formed with 155 g of Eudragite lacquer solution, whereupon it is dried at 40° C., regranulated and homogenized with a powder mixture of 20 g of talc and 20 g of magnesium stearate. Tablets weighing 200 mg and containing 75 mg of active ingredient are pressed in a known manner.

EXAMPLE 110

1500 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-yl-acetic acid, 1500 g of crystalline cellulose, 250 g of polyvinyl pyrolidone are admixed in powdered form in a homogenisator. The powder mixture is granulated with a propanolic solution of 45 g of Eudragit. The granules are dried at 50° C., regranulated and homogenized with a powder mixture of 65 g of talk and 45 g of magnesium stearate. Thus tablets weighing 345 mg and containing 150 mg of the active ingredient are pressed in a known manner. The dragee core thus obtained can be equipped with a film or sugar layer in a known manner.

EXAMPLE 111

100 g of 3-ethoxycarbonyl-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2a)pyrimidine-9-yl-acetic acid are powdered (120 mesh) and homogenized with 5 g of colloidal silicic acid. The powder mixture is uniformly dispersed in 2895 g of molten Witepsol-H at 42° C. From the mass suppositories weighing 3 g and containing 100 g of active ingredient are prepared in a known manner.

The process of Examples 109-111 may also be carried out by using as active ingredient any compound of the formula I in the place of 3-ethoxycarbonyl-6-methyl-4-oxo-4H-pyrido-(1,2a)pyrimidine-9-yl-acetic acid. 

What we claim is:
 1. A compound of the formula ##STR10## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² is hydrogen or hydroxy; R³ is hydrogen, or R² and R³ togehter form a valence bond; R⁶ is trihalomethyl, 5-nitro-2-furyl, 2-furyl, 2-pyrryl, N-methyl-2-pyrryl, phenyl, 3,4,5-trimethoxyphenyl, 3-hydroxy-4-methoxyphenyl, 3,4-methylenedioxyphenyl, dimethoxyphenyl, 4-hydroxyphenyl, 4-chlorophenyl, 4-methoxyphenyl, 2-hydroxyphenyl, 4-dimethylaminophenyl, 2-chlorophenyl, 2-nitrophenyl, 4-nitrophenyl, 2-ethoxyphenyl, 3-nitrophenyl, 3,4-dichlorophenyl, 3-cyanophenyl, 4-N-acetylaminophenyl, or pyridyl; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof.
 2. A compound of the formula: ##STR11## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² is hydrogen or hydroxy; R³ is hydrogen or R² and R³ together form a valence bond; R⁶ is trihalomethyl, pyridyl, phenyl, phenyl substituted by C₁ to C₆ alkyl, dialkylamino wherein the alkyl contains 1 to 6 carbon atoms, nitro, C₁ to C₆ alkoxy, methylenedioxy, cyano or halogen, furyl or pyrryl unsubstituted or substituted by C₁ to C₆ alkyl, nitro, C₁ to C₆ alkoxy, halogen, methylenedioxy, or dialkylamino wherein the alkyl contains 1 to 6 carbon atoms; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof.
 3. 6-methyl-9-(N-methyl-2-pyrryl)-methylene-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine-3-carboxylic acid ethyl ester, as defined in claim
 1. 4. 6-methyl-9-(4-chloro-phenyl)-methylene-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine-3-carboxylic acid ethyl ester, as defined in claim
 1. 5. 9-(carboxy-methyl)-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido(1,2-a)-pyrimidine-3-carboxylic acid ethyl ester.
 6. 9-(methoxycarbonyl-methylene)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine-3-carboxylic acid methyl ester.
 7. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition a compound of the formula: ##STR12## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² is hydrogen or hydroxy; R³ is hydrogen, or R² and R³ together form a valence bond; R⁶ is carboxy, C₁ to C₆ alkoxycarbonyl; 5-nitro-2-furyl, 2-furyl, 2-pyrryl, N-methyl-2-pyrryl, phenyl, 3,4,5-trimethoxyphenyl, 3-hydroxy-4-methoxyphenyl, 3,4-methylenedioxyphenyl, dimethoxyphenyl, 4-hydroxyphenyl, 4-chlorophenyl, 4-methoxyphenyl, 2-hydroxyphenyl, 4-dimethylaminophenyl, 2-chlorophenyl, 2-nitrophenyl, 4-nitrophenyl, 2-ethoxyphenyl, 3-nitrophenyl, 3,4-dichlorophenyl, 3-cyanophenyl, 4-N-acetylaminophenyl, or pyridyl; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable inert carrier.
 8. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition a compound of the formula: ##STR13## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² is hydrogen or hydroxy; R³ is hydrogen or R² and R³ together form a valence bond; R⁶ is carboxy, C₁ to C₆ alkoxycarbonyl, trihalomethyl, pyridyl, phenyl, phenyl substituted by C₁ to C₆ alkyl, dialkylamino wherein the alkyl contains 1 to 6 carbon atoms, nitro, C₁ to C₆ alkoxy, methylenedioxy, cyano or halogen or furyl or pyrryl unsubstituted or substituted by C₁ to C₆ alkyl, nitro, C₁ to C₆ alkoxy, halogen, methylenedioxy, or dialkylamino wherein the alkyl contains 1 to 6 carbon atoms; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable inert carrier.
 9. A compound of the formula: ##STR14## wherein R is hydrogen, or C₁ to C₆ alkyl in the 6- or 7-position;R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy, C₁ to C₆ alkoxycarbonyl, ##STR15## carbamoyl, phenyl, or methyl; or a pharmaceutically acceptable salt thereof.
 10. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition a compound of the formula: ##STR16## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy, C₁ to C₆ alkoxycarbonyl, ##STR17## carbamoyl, phenyl, or methyl; or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable inert carrier.
 11. A compound of the formula: ##STR18## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R⁶ is phenyl or nitrophenyl; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof.
 12. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition a compound of the formula: ##STR19## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R⁶ is phenyl or nitrophenyl; R⁷ and R⁸ independently represent hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carboxy or C₁ to C₆ alkoxycarbonyl; or a pharmaceutically acceptable salt thereof.
 13. A compound of the formula: ##STR20## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² and R³ are each hydrogen or together form a valence bond; R⁶ is carboxy or C₁ to C₆ alkoxycarbonyl; R⁷ and R⁸ are each hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carbamoyl, phenyl, cyano, or carboethoxymethyl, or a pharmaceutically acceptable salt thereof.
 14. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition a compound of the formula: ##STR21## wherein R is hydrogen or C₁ to C₆ alkyl in the 6- or 7-position;R² and R³ are each hydrogen or together form a valence bond; R⁶ is carboxy or C₁ to C₆ alkoxycarbonyl; R⁷ and R⁸ are each hydrogen or together form a valence bond; R⁹ is hydrogen or C₁ to C₆ alkyl; R¹⁰ is carbamoyl, phenyl, cyano or carboethoxymethyl; or a pharmaceutically acceptable salt thereof.
 15. 3-ethoxycarbonyl-9-(1-hydroxyl-2,2,2-trichloroethyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine or a pharmaceutically acceptable salt thereof.
 16. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition the compound defined in claim 15 or a pharmaceutically acceptable salt thereof.
 17. 3-ethoxycarbonyl-9,9-di-(hydroxymethyl)-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine or a pharmaceutically acceptable salt thereof.
 18. An antiatherosclerotic method of treatment which comprises the step of administering to an animal subject in an effective dosage for a period sufficient to ameliorate the condition the compound defined in claim 17 or a pharmaceutically acceptable salt thereof. 